Low-dose computed tomography for lung screening is able to identify smaller nodules more often than can chest radiographs. However, complications of invasive diagnostic procedures of detected nodules are common in practice. Exosomes, membrane vesicles released from cells, contain a diverse array of biomolecules that closely reflect the biologic state of cell and tissue from which they are released. The presence of exosomes in bronchoalveolar lavage (BAL) fluid in various clinical situations has also been reported. However, little is known about the exosomes in BAL fluid in patients with lung cancer, especially early stage lung cancer. We performed this study to investigate diagnostic values in bronchoalveolar lavage (BAL) fluid exosomal micro (mi)RNA in early stage lung adenocarcinoma. METHODS: We chose candidate miRNAs (miR-7, miR-21, miR-126, Let-7a, miR-17, and miR-19) known as having a diagnostic value of lung adenocarcinoma. Exosomes were isolated from BAL fluid from control subjects (n ¼ 15) and patients with lung adenocarcinoma (n ¼ 13). Exosomal RNA was analyzed by using commercial kit containing probes for selected 6 miRNAs. Results were validated with quantitative RT-PCR. RESULTS: The presence of miRNAs was confirmed in exosomes from BAL fluid of both lung adenocarcinoma patients and control subjects. MiR-126 (p<0.001) and Let-7a (p¼0.015) were present in significantly higher levels in the BAL fluid of lung adenocarcinoma patients than in control subjects. The BAL fluid miRNA signature was confirmed using an independent set of paired adenocarcinoma and normal tissue samples (n ¼ 4). Lung adenocarcinoma tissues showed increased expression of miR-126 (p¼0.039) as compared to normal tissue samples. CONCLUSIONS: We identified that a close correlation between the BAL fluid exosomal miRNAs and tumor miRNAs. BAL fluid exosomal miRNAs obtained by noninvasive methods could serve as diagnostic biomarkers in early stage lung adenocarcinoma. CLINICAL IMPLICATIONS: Recently, it was reported that circulating miRNA in body fluid have diagnostic and prognostic value in various clinical diseases. This study demonstrated that altered miRNA expression in BAL fluid exosmes in early stage lung adenocarcinoma. We suggest that exosomal miRNA from BAL fluid could distingish lung cancer in a noninvasive diagnostic procedure.
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